PROJECT SUMMARY Influenza infection is an important cause of morbidity and mortality. About a third of influenza transmission occurs within households, with household members of infected persons at highest risk of becoming infected. Better understanding of the patterns and timing of influenza infection within households is important to guide policies to prevent and control influenza during both seasonal epidemics and in the event of a pandemic. The aim of this project is to estimate the infection risk and factors associated with infection and transmission among household contacts of persons with confirmed influenza infection. Persons with confirmed influenza infection (index cases) will be identified through ongoing studies of influenza vaccine effectiveness among patients with medically-attended acute respiratory illness of ?7 days duration. Index cases and their household contacts will be eligible for this study if there is at least one other person in the index case?s household and the first person in the household with onset of respiratory illness was in the household in the past 10 days (of study enrollment). Eligible household will have two scheduled home visits (first visit within 2 days of notification of positive results and second visit 5 days after the first visit) and a follow-up phone call. Trained research staff will obtain nasal and throat swabs from all consenting household contacts during the home visits and administer a brief questionnaire to assess demographics, general health status, onset and presence of respiratory symptoms, and relevant exposures. The follow-up call will assess illness resolution and impact on daily activities in ill participants. Influenza immunization status will be determined by a validated immunization registry. The combined nasal and throat swabs from each home visit will be tested for influenza using RT-PCR. Annual risk of secondary transmission in households will be calculated for different age groups and influenza subtypes when possible. Household serial intervals and duration of infectiousness will be estimated using transmission models. Data will be provided to CDC for combined analyses of other participating sites. Respiratory specimens from household transmission pairs will be sent to CDC for genetic characterization and analysis of influenza viral evolution.